Prednisone-Induced Hemostasis in Platelet Function Abnormality
a
John J. Hutter, Jr., MD, William E. Hathaway, MD
A 6-year-old girl had chronic thrombocytopenia and substantial platelet function abnormality associated with detectable IgM antiplatelet antibody. Treatment with prednisone was followed by an improvement in bleeding time, although in vitro platelet
function deteriorated. This observation suggests an effect of prednisone on hemostasis that is independent of platelet function. Further trials of prednisone in patients with similar platelet function abnormalities who have a substantial bleeding tendency would appear indicated.
prednisone plateletvessel interaction Thebleeding patients with effect of
on
and small ves¬ in thromsel bocytopenia is poorly understood. Prednisone has been asserted to have a nonspecific effect on bleeding by in¬ creasing vascular resistance in pa¬ tients with any form of thrombocytopenia, and the clinical observation has been made that purpura may be re¬ duced even when the platelet count remains unaltered.1 The correlation of changes after steroid therapy in the bleeding time and clinical hemostasis with platelet count and platelet function tests in patients with thrombocytopenia and platelet function ab¬ normalities provides further insight into this effect. Received for
cepted Aug
publication May 28, 1974;
ac-
14.
From the Department of Pediatrics, University of Colorado Medical Center, Denver. Reprint requests to Department of Pediatrics, University of Colorado Medical Center, 4200 E Ninth Ave, Denver, CO 80220 (Dr. Hathaway).
The patient described here had chronic thrombocytopenic purpura as¬ sociated with a transiently detectable IgM antiplatelet antibody and poor platelet function. Prednisone treat¬ ment produced an improvement in the patient's bleeding time but paradox¬ ically was associated with a worsen¬ ing of in vitro platelet function. REPORT OF A CASE A 6-year-old girl had bruising and a platelet count of 45,000/cu mm in April of 1970. After two weeks of prednisone therapy, her platelet count increased to mm, but then fell to 59,000/cu after cessation of therapy. During the next two years the platelet count ranged from 100,000 to 150,000/cu mm. In September of 1972, the patient devel¬ oped a maxillary cyst that required surgi¬ cal removal. Because of her past history of easy bruisability and persistent thrombocytopenia, she was referred to the Uni¬ versity of Colorado Medical Center for ex¬ amination in December of 1972. There was no family history of bleeding tendency. Results of physical examination were normal, with the exception of ecchymoses on the legs and arms. No splenomegaly was present. Hemoglobin level was 13.6 gm/100 ml and the white blood cell (WBC) count was 7,600/cu mm. The platelet count was 170,000/cu mm and the platelets ap¬ peared morphologically normal on the smear. An Ivy bleeding time was 12% min¬
121,000/cu
mm
(normal two to seven minutes), partial thromboplastin time was 45 seconds (nor¬ mal 37 to 50 seconds), factor VIII level was 80%, and the prothrombin and thrombin times were normal. Because of the history of chronic thrombocytopenia and the pro-
utes
longed bleeding time with a low normal platelet count, platelet antibody studies and in vitro platelet function tests were performed (Table 1). Serum immunoglobulin levels were normal for the child's age; antinuclear antibody test was negative. After detection of serum antiplatelet an¬ tibody plus verification of abnormal in vitro platelet function, the patient (whose surface area was 1.0 sq m) was given pred¬ nisone, 40 mg/day orally for five weeks. On return of the bleeding time to normal, the dose was gradually reduced to 10 mg/ day for two weeks; the bleeding time re¬ mained normal. The maxillary cyst was re¬ moved while the patient was receiving this reduced dosage of prednisone without ex¬ cessive bleeding. On completion of the op¬ eration, prednisone therapy was discontin¬ ued and the bleeding time increased. At no time during her course had the patient taken aspirin or any drug known to inhibit platelet function.
METHODS Tests to determine number of platelets; Ivy bleeding time; platelet adhesiveness to glass beads; platelet aggregation to adencsine diphosphate (ADP), i-epinephrine, and collagen; and platelet factor 3 release to ADP were performed according to meth¬
ods detailed previously.2· ' The titer of fi¬ brin split products was determined by a modification of the RBC hemagglutination inhibition assay.4 The effect of the patient's platelet-poor plasma on the aggregation of normal platelets was tested in the following man¬ ner. Two parts of platelet-rich plasma from a normal donor were mixed with one part of fresh platelet-poor plasma from the patient to yield a final platelet count of 200,000/cu mm and incubated at 37 C for
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/30/2015
Table 1.—Platelet
Antibody and Platelet Function Studies % Total
Platelet
Bleeding
Date
12/1/72 12/28/72 2/13/73 2/27/73
Time, min Treatment None None None
Prednisone, mg/sq m/day Prednisone,
(2-7)* 12V2 >15 20
Patient Platelet Factor 3 Release to
Aggregations!
(89.0 ± 4)
Collagen (92.0 ± 5)
f-Epinephrine (88.0 ± 12)t
ND
ND 79 88 ND
ND 68 67 ND
ND 44 65 ND
ND 6.5 ND ND
325,000
81
30
25
3.0
ND
ND
ND
ND
ND
140,000 110,000
100
68 ND
48 ND
6.8 ND
Platelets
/cu
mm
ADP
170,000 200,000 120,000
ADP, sec§
40
3/21/73 3/29/73 6/21/73 12/27/73
40
mg/sq m/day
6%
Prednisone, 10 mg/sq None None
m/day >15 >15
ND
* Normal values are given in parentheses. t Percent total change in optical density. t Normal mean ± SD. § Expressed as decrease in Russell Viper Venon time (normal >8.0 sec).
II Not done.
30 minutes. The resulting mixture was ob¬ served for spontaneous aggregation in ad¬ dition to aggregation with ADP, Z-epinephrine, and collagen. The aggregation curves obtained were compared to those of the normal donor platelets tested in an identi¬ cal fashion. Serum from the patient that had been inactivated at 56 C for 30 minutes was used to determine platelet antibody by a modification of the platelet factor 3 release method described by Horowitz and others.5 This method is based on the shortening of Russell Viper Venom recalcification time by platelet factor 3 released by the reac¬ tion of platelets with platelet antibody. A mixture of 0.45 ml of normal donor plate¬ let-rich plasma (platelet concentration 500,000/cu mm) and 0.05 ml of inactivated serum was incubated for 30 minutes at 37 C. To each of four 0.1-ml aliquote of this in¬ cubation mixture is added 0.2 ml of a mix¬ ture consisting of equal parts of 0.025M calcium chloride and 1:250,000 Stypven rea¬ gent at 37 C in a fibrometer. The Russell Viper Venom time for normal serum in our laboratory by this method is approxi¬ mately 40 seconds, and the standard error of the mean for the quadruplicate determi¬ nations is less than 1.5 seconds. A result is considered positive if the test serum yields a Russell Viper Venom time of less than 35 seconds and is also more than five seconds shorter than that of a simultaneously run normal serum. Positive serum was diluted 1:1 with Veronal buffer pH 7.34 (control) or mixed with an equal volume of goat antihuman IgG or goat anti-human IgM se¬ rum. After incubation for one hour at 37 C, the mixtures were refrigerated at 4 C overnight and the resulting precipitates were removed by centrifugation. Super-
Dec Jan Feb March June April May Response of in vivo bleeding time (upper line) and in vitro collagen aggregatic line) to prednisone administration (black area).
natante were then tested for their to release platelet factor 3.
ability
RESULTS
The results of the sequential stud¬ ies are presented in Table 1. When the patient was receiving prednisone, there was a substantial reduction in bleeding time to within normal limits and a slight increase in platelet count. Paradoxically, in vitro platelet function as measured by ADP-induced platelet factor 3 release and platelet
aggregation to ADP, ¿-epinephrine, collagen worsened, while the bleeding time improved during the and
administration of
ure).
prednisone (Fig¬
A factor that released
platelet fac¬ platelets was con¬ sistently detectable in several repli¬
tor 3 from normal
cate assays from the
serum
obtained
(Dec 28, 1972) and sub¬ sequently spontaneously disappeared. on one
date
The effect of this serum factor was completely neutralized by goat antihuman IgM serum, demonstrating that an IgM antiplatelet antibody component was present transiently in this patient (Table 2). The patient's plasma on three separate occasions had no effect on the in vitro function
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/30/2015
Table 2.—Demonstration of IgM Component of Serum Antiplatelet Factor Russell
Viper Venom Time, sec
_A_
Normal PRPf + normal serum
Normal PRP + patient serum
Normal PRP+ normal serum + anti IgM Normal PRP + patient serum + anti IgM
Mean
SE*
40.7
1.3
31.6
1.0
40.4
1.5
39.7
1.1
SE for quadruplicate determinations, t Normal platelet-rich plasma contains 500,000 platelets per cubic millimeter. *
of normal platelets. Fibrin split product determinations were performed at the time of plate¬ let function studies and were nega¬ tive on each occasion. Platelet adhe¬ siveness to glass beads was normal prior to prednisone therapy and re¬ mained normal during therapy. COMMENT
Our patient whose platelet count had persisted in the low normal to normal range had a decrease in bleed¬ ing time and tolerated a surgical pro¬ cedure while receiving prednisone. The slight rise in platelet count ob¬ served after prednisone administra¬ tion does not in itself explain the in vivo improvement, as on another oc¬ casion prior to receiving prednisone, the patient has a severely abnormal bleeding time associated with a nor¬ mal platelet count of 200,000/cu mm. Corticosteroids have previously been described to be inhibitors of in vitro platelet function,6 and the adminis-
tration of prednisone to our patient was associated with an increased ab¬ normality in platelet aggregation to ADP, collagen, and ¿-epinephrine in vitro. The ADP-induced platelet fac¬ tor 3 release was also further im¬ paired. The return of the bleeding time and platelet function abnormal¬ ities to pretreatment levels after prednisone treatment was discontin¬ ued is strongly suggestive that the response observed was due to the ef¬ fect of the drug rather than a sponta¬ neous
change.
An antiplatelet antibody that in¬ duced the release of platelet factor 3 from the platelets of a normal indi¬ vidual was detected in the serum of the patient. The neutralization of this antiplatelet factor by specific IgM an¬ tisera demonstrates that there was an
IgM antibody component present,
which establishes the diagnosis of au¬ toimmune thrombocytopenia purpura. Autoimmune thrombocytopenia sec¬ ondary to IgG antibodies is well rec¬ ognized.78 Although IgM antibodies have not been previously noted as a cause of autoimmune thrombocyto¬ penia, an IgM component of antibody has been described in association with a drug-induced antiplatelet anti¬
body.10 Qualitative abnormalities in plate¬ let aggregation similar to those ob¬ served in our patient have been de¬ scribed in patients with chronic idiopathic thrombocytopenia purpura (ITP) in remission who had slightly depressed platelet counts." Thus, the most likely cause of the platelet func¬ tion defect in our patient is that it is secondary to an autoimmune throm¬ bocytopenia. The possibility of an as-
sociated congenital platelet function defect has not been completely ex¬ cluded, but there is no family history of bleeding tendency. Autoimmune an¬ tiplatelet antibodies have also been described in patients with systemic lupus erythematosis, but this diag¬ nosis is unlikely due to the absence of detectable antinuclear antibody. In a previous series, the severity of the platelet function defect in chronic ITP did not correlate with the pres¬ ence of antiplatelet antibody as de¬ tected by the platelet factor 3 assay.8 In contrast to the results described by Clancy et al,8 the patient's plasma had no effect on the aggregation of normal donor platelets on several oc¬ casions. The possibility remains, how¬ ever, that an antiplatelet factor with high affinity for the patient's plate¬ lets was present, so that the majority of factor was bound to platelets rather than free in the plasma. The data in this case would suggest that the effect of prednisone on bleed¬ ing time is mediated at least in part through improvement in vessel hemostasis, which is independent of its ef¬ fect on circulating platelet number or function. A short-term trial of pred¬ nisone would appear to be indicated in patients with a platelet function abnormality associated with anti¬ platelet antibody who have a substan¬ tial clinical bleeding problem. This investigation was supported in part by Pediatrie Oncology Center grant 3 PO 2 CA12247-03. Carolyn Borden provided technical assistance.
Nonproprietary Name and Trademark of Drug Prednisone-Afeíicoríew.
References 1. Baldini MG: Idiopathic thrombocytopenic purpura and the ITP syndrome. Med
Clin North Am 56:47-64, 1972. 2. Call KE, Mull MM, Hathaway WE: Platelet function in classic (AHF deficiency) hemophilia: Report of a case with defective platelet function. Blood 33:26-36, 1969. 3. Hathaway
WE, Solomons CC, Ott JE: Platelet function and pyrophosphates in osteogenesis imperfecta. Blood 39:500-509,
1972. 4. Mertens BF, McDuffie SC, Bowie EJ, et al: Rapid sensitive method for measuring fibrinogen split products in human se-
Mayo Clin Proc 44:114-120, 1969. 5. Horowitz HI, Rappaport HI, Young RC, et al: Change in platelet factor 3 as a means of demonstrating immune reactions involving platelets: Its use as a test for quinidine-induced thrombocytopenia.
rum.
Transfusion 5:336-343, 1965. 6. Molinas F, Kaulla KN von: On the effect of human thrombocytes of synthetic organic fibrinolytic compounds. Thromb Diath Haemorrh 21:46-64, 1969. 7. Karpatkin S, Siskind GW: In vitro detection of platelet antibody in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosis. Blood
33:795-812, 1969. 8. Clancy R, Jenkins E, Firkin B: Qual-
platelet abnormalities in idiopathic thrombocytopenic purpura. N Engl J Med 286:622-626, 1972. 9. Handin RI, Stossel TP: Phagocytosis of antibody-coated platelets by human granulocytes. N Engl J Med 290:989-993, 1974. 10. Eisner EV, Korbitz BC: Quinine-induced thrombocytopenic purpura due to an IgM and an IgG antibody. Transfusion itative
12:317-321, 1972.
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/30/2015
a
John J. Hutter, Jr., MD, William E. Hathaway, MD
A 6-year-old girl had chronic thrombocytopenia and substantial platelet function abnormality associated with detectable IgM antiplatelet antibody. Treatment with prednisone was followed by an improvement in bleeding time, although in vitro platelet
function deteriorated. This observation suggests an effect of prednisone on hemostasis that is independent of platelet function. Further trials of prednisone in patients with similar platelet function abnormalities who have a substantial bleeding tendency would appear indicated.
prednisone plateletvessel interaction Thebleeding patients with effect of
on
and small ves¬ in thromsel bocytopenia is poorly understood. Prednisone has been asserted to have a nonspecific effect on bleeding by in¬ creasing vascular resistance in pa¬ tients with any form of thrombocytopenia, and the clinical observation has been made that purpura may be re¬ duced even when the platelet count remains unaltered.1 The correlation of changes after steroid therapy in the bleeding time and clinical hemostasis with platelet count and platelet function tests in patients with thrombocytopenia and platelet function ab¬ normalities provides further insight into this effect. Received for
cepted Aug
publication May 28, 1974;
ac-
14.
From the Department of Pediatrics, University of Colorado Medical Center, Denver. Reprint requests to Department of Pediatrics, University of Colorado Medical Center, 4200 E Ninth Ave, Denver, CO 80220 (Dr. Hathaway).
The patient described here had chronic thrombocytopenic purpura as¬ sociated with a transiently detectable IgM antiplatelet antibody and poor platelet function. Prednisone treat¬ ment produced an improvement in the patient's bleeding time but paradox¬ ically was associated with a worsen¬ ing of in vitro platelet function. REPORT OF A CASE A 6-year-old girl had bruising and a platelet count of 45,000/cu mm in April of 1970. After two weeks of prednisone therapy, her platelet count increased to mm, but then fell to 59,000/cu after cessation of therapy. During the next two years the platelet count ranged from 100,000 to 150,000/cu mm. In September of 1972, the patient devel¬ oped a maxillary cyst that required surgi¬ cal removal. Because of her past history of easy bruisability and persistent thrombocytopenia, she was referred to the Uni¬ versity of Colorado Medical Center for ex¬ amination in December of 1972. There was no family history of bleeding tendency. Results of physical examination were normal, with the exception of ecchymoses on the legs and arms. No splenomegaly was present. Hemoglobin level was 13.6 gm/100 ml and the white blood cell (WBC) count was 7,600/cu mm. The platelet count was 170,000/cu mm and the platelets ap¬ peared morphologically normal on the smear. An Ivy bleeding time was 12% min¬
121,000/cu
mm
(normal two to seven minutes), partial thromboplastin time was 45 seconds (nor¬ mal 37 to 50 seconds), factor VIII level was 80%, and the prothrombin and thrombin times were normal. Because of the history of chronic thrombocytopenia and the pro-
utes
longed bleeding time with a low normal platelet count, platelet antibody studies and in vitro platelet function tests were performed (Table 1). Serum immunoglobulin levels were normal for the child's age; antinuclear antibody test was negative. After detection of serum antiplatelet an¬ tibody plus verification of abnormal in vitro platelet function, the patient (whose surface area was 1.0 sq m) was given pred¬ nisone, 40 mg/day orally for five weeks. On return of the bleeding time to normal, the dose was gradually reduced to 10 mg/ day for two weeks; the bleeding time re¬ mained normal. The maxillary cyst was re¬ moved while the patient was receiving this reduced dosage of prednisone without ex¬ cessive bleeding. On completion of the op¬ eration, prednisone therapy was discontin¬ ued and the bleeding time increased. At no time during her course had the patient taken aspirin or any drug known to inhibit platelet function.
METHODS Tests to determine number of platelets; Ivy bleeding time; platelet adhesiveness to glass beads; platelet aggregation to adencsine diphosphate (ADP), i-epinephrine, and collagen; and platelet factor 3 release to ADP were performed according to meth¬
ods detailed previously.2· ' The titer of fi¬ brin split products was determined by a modification of the RBC hemagglutination inhibition assay.4 The effect of the patient's platelet-poor plasma on the aggregation of normal platelets was tested in the following man¬ ner. Two parts of platelet-rich plasma from a normal donor were mixed with one part of fresh platelet-poor plasma from the patient to yield a final platelet count of 200,000/cu mm and incubated at 37 C for
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/30/2015
Table 1.—Platelet
Antibody and Platelet Function Studies % Total
Platelet
Bleeding
Date
12/1/72 12/28/72 2/13/73 2/27/73
Time, min Treatment None None None
Prednisone, mg/sq m/day Prednisone,
(2-7)* 12V2 >15 20
Patient Platelet Factor 3 Release to
Aggregations!
(89.0 ± 4)
Collagen (92.0 ± 5)
f-Epinephrine (88.0 ± 12)t
ND
ND 79 88 ND
ND 68 67 ND
ND 44 65 ND
ND 6.5 ND ND
325,000
81
30
25
3.0
ND
ND
ND
ND
ND
140,000 110,000
100
68 ND
48 ND
6.8 ND
Platelets
/cu
mm
ADP
170,000 200,000 120,000
ADP, sec§
40
3/21/73 3/29/73 6/21/73 12/27/73
40
mg/sq m/day
6%
Prednisone, 10 mg/sq None None
m/day >15 >15
ND
* Normal values are given in parentheses. t Percent total change in optical density. t Normal mean ± SD. § Expressed as decrease in Russell Viper Venon time (normal >8.0 sec).
II Not done.
30 minutes. The resulting mixture was ob¬ served for spontaneous aggregation in ad¬ dition to aggregation with ADP, Z-epinephrine, and collagen. The aggregation curves obtained were compared to those of the normal donor platelets tested in an identi¬ cal fashion. Serum from the patient that had been inactivated at 56 C for 30 minutes was used to determine platelet antibody by a modification of the platelet factor 3 release method described by Horowitz and others.5 This method is based on the shortening of Russell Viper Venom recalcification time by platelet factor 3 released by the reac¬ tion of platelets with platelet antibody. A mixture of 0.45 ml of normal donor plate¬ let-rich plasma (platelet concentration 500,000/cu mm) and 0.05 ml of inactivated serum was incubated for 30 minutes at 37 C. To each of four 0.1-ml aliquote of this in¬ cubation mixture is added 0.2 ml of a mix¬ ture consisting of equal parts of 0.025M calcium chloride and 1:250,000 Stypven rea¬ gent at 37 C in a fibrometer. The Russell Viper Venom time for normal serum in our laboratory by this method is approxi¬ mately 40 seconds, and the standard error of the mean for the quadruplicate determi¬ nations is less than 1.5 seconds. A result is considered positive if the test serum yields a Russell Viper Venom time of less than 35 seconds and is also more than five seconds shorter than that of a simultaneously run normal serum. Positive serum was diluted 1:1 with Veronal buffer pH 7.34 (control) or mixed with an equal volume of goat antihuman IgG or goat anti-human IgM se¬ rum. After incubation for one hour at 37 C, the mixtures were refrigerated at 4 C overnight and the resulting precipitates were removed by centrifugation. Super-
Dec Jan Feb March June April May Response of in vivo bleeding time (upper line) and in vitro collagen aggregatic line) to prednisone administration (black area).
natante were then tested for their to release platelet factor 3.
ability
RESULTS
The results of the sequential stud¬ ies are presented in Table 1. When the patient was receiving prednisone, there was a substantial reduction in bleeding time to within normal limits and a slight increase in platelet count. Paradoxically, in vitro platelet function as measured by ADP-induced platelet factor 3 release and platelet
aggregation to ADP, ¿-epinephrine, collagen worsened, while the bleeding time improved during the and
administration of
ure).
prednisone (Fig¬
A factor that released
platelet fac¬ platelets was con¬ sistently detectable in several repli¬
tor 3 from normal
cate assays from the
serum
obtained
(Dec 28, 1972) and sub¬ sequently spontaneously disappeared. on one
date
The effect of this serum factor was completely neutralized by goat antihuman IgM serum, demonstrating that an IgM antiplatelet antibody component was present transiently in this patient (Table 2). The patient's plasma on three separate occasions had no effect on the in vitro function
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/30/2015
Table 2.—Demonstration of IgM Component of Serum Antiplatelet Factor Russell
Viper Venom Time, sec
_A_
Normal PRPf + normal serum
Normal PRP + patient serum
Normal PRP+ normal serum + anti IgM Normal PRP + patient serum + anti IgM
Mean
SE*
40.7
1.3
31.6
1.0
40.4
1.5
39.7
1.1
SE for quadruplicate determinations, t Normal platelet-rich plasma contains 500,000 platelets per cubic millimeter. *
of normal platelets. Fibrin split product determinations were performed at the time of plate¬ let function studies and were nega¬ tive on each occasion. Platelet adhe¬ siveness to glass beads was normal prior to prednisone therapy and re¬ mained normal during therapy. COMMENT
Our patient whose platelet count had persisted in the low normal to normal range had a decrease in bleed¬ ing time and tolerated a surgical pro¬ cedure while receiving prednisone. The slight rise in platelet count ob¬ served after prednisone administra¬ tion does not in itself explain the in vivo improvement, as on another oc¬ casion prior to receiving prednisone, the patient has a severely abnormal bleeding time associated with a nor¬ mal platelet count of 200,000/cu mm. Corticosteroids have previously been described to be inhibitors of in vitro platelet function,6 and the adminis-
tration of prednisone to our patient was associated with an increased ab¬ normality in platelet aggregation to ADP, collagen, and ¿-epinephrine in vitro. The ADP-induced platelet fac¬ tor 3 release was also further im¬ paired. The return of the bleeding time and platelet function abnormal¬ ities to pretreatment levels after prednisone treatment was discontin¬ ued is strongly suggestive that the response observed was due to the ef¬ fect of the drug rather than a sponta¬ neous
change.
An antiplatelet antibody that in¬ duced the release of platelet factor 3 from the platelets of a normal indi¬ vidual was detected in the serum of the patient. The neutralization of this antiplatelet factor by specific IgM an¬ tisera demonstrates that there was an
IgM antibody component present,
which establishes the diagnosis of au¬ toimmune thrombocytopenia purpura. Autoimmune thrombocytopenia sec¬ ondary to IgG antibodies is well rec¬ ognized.78 Although IgM antibodies have not been previously noted as a cause of autoimmune thrombocyto¬ penia, an IgM component of antibody has been described in association with a drug-induced antiplatelet anti¬
body.10 Qualitative abnormalities in plate¬ let aggregation similar to those ob¬ served in our patient have been de¬ scribed in patients with chronic idiopathic thrombocytopenia purpura (ITP) in remission who had slightly depressed platelet counts." Thus, the most likely cause of the platelet func¬ tion defect in our patient is that it is secondary to an autoimmune throm¬ bocytopenia. The possibility of an as-
sociated congenital platelet function defect has not been completely ex¬ cluded, but there is no family history of bleeding tendency. Autoimmune an¬ tiplatelet antibodies have also been described in patients with systemic lupus erythematosis, but this diag¬ nosis is unlikely due to the absence of detectable antinuclear antibody. In a previous series, the severity of the platelet function defect in chronic ITP did not correlate with the pres¬ ence of antiplatelet antibody as de¬ tected by the platelet factor 3 assay.8 In contrast to the results described by Clancy et al,8 the patient's plasma had no effect on the aggregation of normal donor platelets on several oc¬ casions. The possibility remains, how¬ ever, that an antiplatelet factor with high affinity for the patient's plate¬ lets was present, so that the majority of factor was bound to platelets rather than free in the plasma. The data in this case would suggest that the effect of prednisone on bleed¬ ing time is mediated at least in part through improvement in vessel hemostasis, which is independent of its ef¬ fect on circulating platelet number or function. A short-term trial of pred¬ nisone would appear to be indicated in patients with a platelet function abnormality associated with anti¬ platelet antibody who have a substan¬ tial clinical bleeding problem. This investigation was supported in part by Pediatrie Oncology Center grant 3 PO 2 CA12247-03. Carolyn Borden provided technical assistance.
Nonproprietary Name and Trademark of Drug Prednisone-Afeíicoríew.
References 1. Baldini MG: Idiopathic thrombocytopenic purpura and the ITP syndrome. Med
Clin North Am 56:47-64, 1972. 2. Call KE, Mull MM, Hathaway WE: Platelet function in classic (AHF deficiency) hemophilia: Report of a case with defective platelet function. Blood 33:26-36, 1969. 3. Hathaway
WE, Solomons CC, Ott JE: Platelet function and pyrophosphates in osteogenesis imperfecta. Blood 39:500-509,
1972. 4. Mertens BF, McDuffie SC, Bowie EJ, et al: Rapid sensitive method for measuring fibrinogen split products in human se-
Mayo Clin Proc 44:114-120, 1969. 5. Horowitz HI, Rappaport HI, Young RC, et al: Change in platelet factor 3 as a means of demonstrating immune reactions involving platelets: Its use as a test for quinidine-induced thrombocytopenia.
rum.
Transfusion 5:336-343, 1965. 6. Molinas F, Kaulla KN von: On the effect of human thrombocytes of synthetic organic fibrinolytic compounds. Thromb Diath Haemorrh 21:46-64, 1969. 7. Karpatkin S, Siskind GW: In vitro detection of platelet antibody in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosis. Blood
33:795-812, 1969. 8. Clancy R, Jenkins E, Firkin B: Qual-
platelet abnormalities in idiopathic thrombocytopenic purpura. N Engl J Med 286:622-626, 1972. 9. Handin RI, Stossel TP: Phagocytosis of antibody-coated platelets by human granulocytes. N Engl J Med 290:989-993, 1974. 10. Eisner EV, Korbitz BC: Quinine-induced thrombocytopenic purpura due to an IgM and an IgG antibody. Transfusion itative
12:317-321, 1972.
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/30/2015
